Liver Transplantation: Skeletal Effects

Skeletal Effects of Liver Transplantation

Fifty patients awaiting liver transplantation and 50 age and gender matched control subjects with normal liver function will be included in the study. The aim of this project is to compare liver transplantation recipients'bone microarchitecture with healthy controls and to evaluate patients' changes within one year after transplantation

Study Overview

• Status: Withdrawn
• Conditions: Liver Diseases; Osteoporosis; Transplant-Related Disorder

Detailed Description

Background: Solid organ transplantation recipients have a high prevalence of osteoporosis and fragility fractures. Deteriorated bone architecture has been shown by high resolution computed tomography (HR-pQCT) in kidney and lung transplantation recipients. In liver transplantation (LeTx) recipients, bone microarchitecture has only been evaluated using the trabecular bone score in a retrospective cohort study; a degraded or partially degraded microarchitecture was detected in most of the patients.

Aim: The aim of this project is to compare LeTx recipients' bone microarchitecture with healthy controls and to evaluate patients' changes within one year after transplantation.

Methods: HR-pQCT scans of the distal radius and tibia as well as areal bone mineral density measurement of the lumbar spine and hip region will be performed before Tx, 1 and 12 months after Tx in 50 patients. Anabolic and catabolic markers of bone turnover (sclerostin, dickkopf 1, periostin) and traditional bone turnover markers will be evaluated preoperatively, on the day of surgery, and 4 times within the first year after LeTx. In healthy age- and sex-matched controls HR-pQCT, bone mineral density and laboratory parameters will be assessed once.

Hypotheses: Based on the HR-pQCT data of kidney and lung transplantation recipients and the trabecular bone score of LeTx recipients, the investigators hypothesize that LeTX recipients have deteriorated bone microarchitecture.

Expected outcome: Since bone fragility is not only determined by BMD but bone architecture as well, HR-pQCT data give important information on the patients' bone fragility. The knowledge of the course of bone microarchitecture after liver transplantation may help to develop strategies preventing fragility fractures in LeTx recipients.

• Study Type: Observational

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

50 patients awaiting liver transplantation and 50 age and gender matched healthy controls

Description

Inclusion Criteria:

• Women, men awaiting liver Transplantation
• 20-70 years of age

Exclusion Criteria:

• Subjects with a history of prior solid organ transplantation
• Subjects awaiting a combined liver-kidney transplantation
• Cancer within the previous 5 years - except for hepatocellular carcinoma, neuroendocrine tumors and hemangioendothelioma with indication for liver transplantation
• Rheumatoid arthritis
• Severe renal insufficiency (chronic kidney disease IV, V)
• Immobilisation
• Intake of drugs with potential effects on BMD like lithium, estrogen-replacement therapy, selective Estrogen-receptor modulators, oral bisphosphonates in the last three months, denosumab and parenteral bisphosphonates in the last year - except calcium, vitamin D and medication necessary for the underlying disease
• Non-osteoporotic bone disease
• Recent fragility fracture within 6 months

Control group:

Inclusion Criteria:

• Women, men
• 20-70 years of age
• Normal liver function (defined as liver function parameters and transaminases, such as albumin, thromboplastin time, alanine-aminotransferase, aspartate-aminotransferase, and gamma-glutamyl-transferase within the normal range)

Additional exclusion Criteria:

• Osteoporosis according to BMD measurement or osteopenia plus fragility fracture
• Liver disease (defined as evidence of significant liver disease according to laboratory testing)

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Liver transplantation recipients; Venipuncture (6x) Bone mineral density measurement: lumbar spine, hip region (3x) high resolution peripheral quantitative CT: radius, tibia (3x)
Control group; Venipuncture (1x) Bone mineral density measurement: lumbar spine, hip region (1x) high resolution peripheral quantitative CT: radius, tibia (1x)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone microarchitecture of the distal radius	trabecular bone mineral density measurement (XCT)	12 months to posttransplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone microarchitecture of the distal radius	bone volume fraction (%)	pretransplantation to 12 after transplantation
Bone microarchitecture of the distal radius	trabecular homogeneity (mm)	pretransplantation to 12 after transplantation
Bone microarchitecture of the distal radius	trabecular number (mm-1)	pretransplantation to 12 after transplantation
Bone microarchitecture of the distal radius	trabecular thickness (mm)	pretransplantation to 12 after transplantation
Bone microarchitecture of the distal radius	trabecular separation (mm)	pretransplantation to 12 months after transplantation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone mineral density	areal bone density measurement of the lumbar spine (T score)	pretransplantation to 12 after transplantation
Bone mineral density	areal bone density measurement of the hip region (T score)	pretransplantation to 12 after transplantation
Biochemical	Serum levels of osteocalcin	pretransplantation to 12 after transplantation
Biochemical	Serum levels of bone-specific alkaline phosphatase	pretransplantation to 12 after transplantation
Biochemical	Serum levels of procollagen type 1 amino-terminal propeptide	pretransplantation to 12 after transplantation
Biochemical	Serum levels of tartrate resistant acid phosphatase	pretransplantation to 12 after transplantation
Biochemical	Serum levels of carboxy-terminal collagen crosslinks	pretransplantation to 12 after transplantation
Biochemical	Serum levels of dickkopf 1	pretransplantation to 12 after transplantation
Biochemical	Serum levels of periostin	pretransplantation to 12 after transplantation
Biochemical	Serum levels of sclerostin	pretransplantation to 12 after transplantation

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Katharina Kerschan-Schindl, MD, Medical University of Vienna

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2020
• Primary Completion (Anticipated): March 31, 2023
• Study Completion (Anticipated): March 31, 2023

Study Registration Dates

• First Submitted: January 5, 2018
• First Submitted That Met QC Criteria: January 12, 2018
• First Posted (Actual): January 16, 2018

Study Record Updates

• Last Update Posted (Actual): September 11, 2020
• Last Update Submitted That Met QC Criteria: September 9, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Bone microarchitecture
• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Liver Diseases; Osteoporosis
• Other Study ID Numbers: 1713/2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No